Hampson Lisa V, Whitehead John, Eleftheriou Despina, Tudur-Smith Catrin, Jones Rachel, Jayne David, Hickey Helen, Beresford Michael W, Bracaglia Claudia, Caldas Afonso, Cimaz Rolando, Dehoorne Joke, Dolezalova Pavla, Friswell Mark, Jelusic Marija, Marks Stephen D, Martin Neil, McMahon Anne-Marie, Peitz Joachim, van Royen-Kerkhof Annet, Soylemezoglu Oguz, Brogan Paul A
Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.
Department of Rheumatology, UCL Institute of Child Health, London, United Kingdom.
PLoS One. 2015 Mar 30;10(3):e0120981. doi: 10.1371/journal.pone.0120981. eCollection 2015.
Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa).
A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis.
A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available.
We suggest that the methodological template we propose could be applied to trial design for other rare diseases.
确定罕见病临床试验的样本量通常是不可行的。在这种情况下，贝叶斯方法可用于最大化从临床试验中学到的知识。我们为一项针对罕见的儿童炎性疾病——结节性多动脉炎（MYPAN，霉酚酸酯治疗结节性多动脉炎）的未来贝叶斯随机对照试验征集了专家先验意见。
召开了一次贝叶斯先验意见征集会议。会议就接受环磷酰胺治疗的MYPAN试验患者在6个月内实现疾病缓解的概率以及霉酚酸酯和环磷酰胺的相对疗效征求了意见。专家意见与来自最近完成的一项关于抗中性粒细胞胞浆抗体相关性血管炎的随机对照试验中尚未公开的数据相结合。
一个由15名专家组成的泛欧洲小组参加了意见征集会议。专家们达成的先验共识意见是，接受环磷酰胺或霉酚酸酯治疗的患者在6个月内疾病缓解的最可能率分别为74%和71%。现在将采用这一先验意见，并在获得40名按1:1随机分配至环磷酰胺（CYC）或霉酚酸酯（MMF）组的MYPAN试验数据后，对其进行修正以形成贝叶斯后验意见。
我们建议我们提出的方法模板可应用于其他罕见病的试验设计。
